Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination

Here we deeply profiled the functional humoral immune response induced by CoronaVac and Pfizer/BNT162b2 vaccines. Particularly we analyzed how the vaccine-induced functional responses waned with time and characterized the boosting capacity of the BNT162b2 vaccine, which enhanced the overall humoral responses of CoronaVac primed vaccinees to levels that were higher than the peak responses seen in the recipients vaccinated with two doses of the CoronaVac or BNT162b2 vaccines. We identified that Fc-receptor binding antibodies waned much faster than binding IgG1. Moreover, while antibody functions were induced against Omicron following BNT162b2 vaccination, these responses waned rapidly over time and were not observed in the setting of CoronaVac vaccination. Importantly, mRNA boosting of the CoronaVac response yielded a striking enhancement of functional humoral immunity across VOCs, including Omicron. These data collectively point to marked vaccine platform-based differences in peak functional humoral protection, as well as their distinct waning profiles. This phenotype can be enhanced and, in several cases, functionally expanded by heterologous boosting.